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Medical Sciences	100%

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Effects of base excision repair gene polymorphisms on pancreatic cancer survival

INTERNATIONAL JOURNAL OF CANCER, Issue 8 2007
Donghui Li
Abstract To explore the association between single nucleotide polymorphisms of DNA repair genes and overall survival of patients with pancreatic cancer, we conducted a study in 378 cases of pancreatic adenocarcinoma who were treated at The University of Texas M. D. Anderson Cancer Center between February 1999 and October 2004 and were followed up to April 2006. Genotypes were determined using genomic DNA and the MassCode method. Overall survival was analyzed using the Kaplan,Meier plot, log-rank test and Cox regression. We observed a strong effect of the POLB A165G and T2133C genotypes on overall survival. The median survival time (MST) was 35.7 months for patients carrying at least 1 of the 2 homozygous variant POLB GG or CC genotypes, compared with 14.8 months for those carrying the AA/AG or TT/TC genotypes (p = 0.02, log rank test). The homozygous variants of hOGG1 G2657A, APEX1 D148E and XRCC1 R194W polymorphisms all showed a weak but significant effect on overall survival as demonstrated by either log rank test or multivariate COX regression after adjusting for other potential confounders. In combined genotype analysis, a predominant effect of the POLB homozygous variants on survival was observed. When POLB was not included in the model, a slightly better survival was observed among those carrying none of the adverse genotypes than those carrying at least one of the adverse genotypes. These observations suggest that polymorphisms of base excision repair genes significantly affect the clinical outcome of patients with pancreatic cancer. These observations need to be confirmed in a larger study of homogenous patient population. © 2007 Wiley-Liss, Inc. [source]

Elevated serum heparanase-1 levels in patients with pancreatic carcinoma are associated with poor survival

CANCER, Issue 3 2006
Roderick M. Quiros M.D.
Abstract BACKGROUND It has previously been shown that heparanase-1 (HPR1), an endoglycosidase, is up-regulated in pancreatic carcinoma. The purpose of this study was to test whether serum HPR1 levels in pancreatic carcinoma patients are elevated, and whether higher serum HPR1 levels are associated with a shortened survival. METHODS Serum HPR1 levels in 40 healthy donors, 31 pancreatic carcinoma patients, and 11 patients treated with gemcitabine were measured by a novel enzyme-linked immunoadsorbent assay. HPR1 expression in tumors was analyzed by immunohistochemical staining. Patient overall survival time was determined according to the Kaplan,Meier method, and their difference was evaluated by the log-rank test. A P value < 0.05 was considered statistically significant. RESULTS The mean serum HPR1 activity in pancreatic carcinoma patients was 439 ± 14 units/mL, compared with 190 ± 4 units/mL in the control serum samples from healthy donors. Serum HPR1 levels were significantly higher in patients with HPR1-positive tumors (660 ± 62 units/mL) compared with those with HPR1-negative tumors (241 ± 14 units/mL). The mean survival of 19 pancreatic carcinoma patients with serum HPR1 activity > 300 units/mL was 7.9 ± 0.2 months, whereas the mean survival of 12 patients with serum HPR1 activity < 300 units/mL was 13.3 ± 0.6 months. A Kaplan,Meier plot of the patient survival curve followed by log-rank test revealed that patients in the high serum HPR1 group had a significantly shorter survival compared with those in the low serum HPR1 group. Mean serum HPR1 activity decreased by 64% in 11 pancreatic carcinoma patients after 2 weeks of treatment with gemcitabine. CONCLUSIONS Serum HPR1 activity in pancreatic carcinoma patients was found to be significantly elevated, in particular in those with HPR1-positive tumors. Increased serum HPR1 activity was associated with a shorter survival in patients with pancreatic carcinoma patients. Cancer 2006. © 2005 American Cancer Society. [source]

Elevated Incidence of Posttransplant Erythrocytosis After Simultaneous Pancreas Kidney Transplantation

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2010
G. Guerra
Posttransplant erythrocytosis (PTE) poses a potential risk of thrombosis in kidney transplantation. Clinical observation of our systemically drained simultaneous kidney pancreas transplant (S-SPK) patients showed a higher incidence of PTE and need for phlebotomies. To evaluate the incidence of PTE we analyzed hematocrit (Hct) levels and frequency of phlebotomies in 94 SPK as compared to 174 living donor (LD) recipients and 53 type-I diabetic with kidney transplant only. For study purposes we defined PTE as Hct >50% or the necessity for phlebotomies. Kaplan,Meier plots and Cox proportional hazard models were used to examine the association between the transplant type and PTE. We found an increased incidence of PTE in SPK compared to LD (p < 0.001). In the multivariate model, SPK had a 5-fold risk for the development of PTE (AHR 5.3, 95% CI 1.8, 15.9). The incidence of therapeutic phlebotomy was 13% among SPK patients and 4% in LD kidney recipients; 19 patients altogether. A total of 64 units were phlebotomized (48-SPK and 16-LD). Type I diabetic patients with a kidney transplant showed a 0% incidence of PTE. We observed a greater incidence of PTE and phlebotomies in S-SPK compared to LD with kidney only transplant recipients. [source]

Pretherapy quantitative measurement of circulating Epstein,Barr virus DNA is predictive of posttherapy distant failure in patients with early-stage nasopharyngeal carcinoma of undifferentiated type

CANCER, Issue 2 2003
Sing-fai Leung M.D.
Abstract BACKGROUND Patients with International Union Against Cancer (UICC) Stage I,II nasopharyngeal carcinoma (NPC) appear to have a relatively favorable prognosis and generally are excluded from trials of combined modality treatment. More recently, plasma/serum cell-free Epstein-Barr virus (EBV) DNA has been shown to be measurable in the majority of NPC patients at the time of diagnosis, and appears to have prognostic significance. However, within Stage I-II disease, in which failure events are infrequent, the prognostic impact of the pretreatment EBV DNA level has not been addressed to our knowledge. This issue has management implications because different therapeutic strategies currently are employed for patients with good-risk and those with poor-risk NPC. METHODS A cohort of 90 patients with UICC Stage I-II NPC (World Health Organization Grade 2/3 histology) had their pretherapy plasma/serum EBV DNA levels determined by a quantitative polymerase chain reaction assay and correlated with the probability of posttherapy failure. All patients received radiation therapy only, except for three patients who also received concurrent chemotherapy. Kaplan,Meier plots of the probability of locoregional failure, distant failure, and cancer-specific survival were compared with reference to clinical stage and EBV DNA levels. RESULTS With a median follow-up time of 45 months, 12 patients and 7 patients, respectively, had developed locoregional and distant failures, including 2 patients with both local and distant failures. Patients with distant failure had significantly higher pretherapy EBV DNA levels than those without failure (a median of 13,219 copies/mL [interquatile-range, 274,635 copies/mL] vs. a median of 423 copies/mL [interquatile-range, 2753 copies/mL]). The probability of distant failure was significantly higher in patients with high (> 4000 copies/mL plasma) compared with low EBV DNA levels (P = 0.0001, log-rank test) and for Stage IIB disease compared with Stage I and Stage IIA disease combined (P = 0.0149, log-rank test), but was not significantly different between patients with Stage II and those with Stage I disease. The risks of locoregional failure were not significantly different between patients with high and those with low EBV DNA levels, and also was not significantly different between clinical substages. Approximately 35% of patients with Stage IIB disease were in the at-risk group for distant failure, as identified by high EBV DNA levels. CONCLUSIONS Within a group of patients with UICC Stage I-II NPC, the pretherapy plasma EBV DNA level was found to identify a poor-risk group with a probability of distant failure similar to that of patients with advanced stage disease. This group of patients may warrant management considerations currently applicable only to cases of Stage III-IV disease. The prognostic significance of designating Stage IIB disease as per the 1997 UICC staging was confirmed, although the pretherapy EBV DNA level appears to be a more powerful prognostic discriminator in patients with early-stage NPC. Cancer 2003;98:288,91. © 2003 American Cancer Society. DOI 10.1002/cncr.11496 [source]